A calcium sensing receptor (CaSR) is also called a calcium receptor, and such receptor signals regulate various in vivo functions. Thus, there is a possibility that substances having a CaSR agonist activity are useful for treating or preventing various diseases and also useful as kokumi-imparting agents. Patent Document 1 discloses a screening method for a kokumi-imparting substance and a kokumi-imparting agent containing a kokumi-imparting substance obtained by the screening method. In the document it is found that a variety of low molecular weight peptides have the CaSR agonist activity. It is disclosed therein that based on this finding, it has become possible to provide a kokumi-imparting agent which can impart “kokumi”, the taste that cannot be expressed only with five basic tastes of sweet, salty, sour, bitter and umami tastes, and the taste that enhances marginal tastes of the basic tastes described above, such as thickness, growth (mouthfulness), continuity and harmony.
On the other hand, it has been known from old that γ-glutamylanilide derivatives act as the substrate for γ-glutamyltransferase, and can be used for enzyme activity measurements (Non-Patent Document 1, Patent Document 2). However, there is no publication that describes the relation of “the calcium sensing receptor (CaSR) or G protein-coupled receptor,” which is a characteristic feature of the present invention, to “kokumi taste,” “diarrhea” or “hyperparathyroidism.” Also in some known compounds of γ-glutamylanilide derivatives which are 3-sulfonic acids, 3-carboxylic acids and 3-nitro derivatives, most of their utilities are focused on substrates in enzyme activity measurements of γ-glutamyltransferase, and use as antibacterial agents or antiallergic agents (Non-Patent Document 2 and Patent Document 3) and use as analysis reagents for mass spectrometry (Non-Patent Document 3) are only known for other uses. Furthermore, Cinacalcet and analogous synthetic low molecular weight compounds and γ-glutamylpeptide derivatives including glutathione are known as CaSR-activating compounds (Patent Document 4 and Non-Patent Documents 4 and 5), but these compounds are structurally different from the glutamate derivatives of the present invention.
Therefore, it is expected to provide more excellent kokumi-imparting agents by searching more varieties of compounds having the CaSR agonist activity. It is also expected to provide CaSR agonist agents, pharmaceutical compositions and preventive or therapeutic agents for diarrhea.